Excitatory amino acids (EAA), such as L-glutamate and L-aspartate, are involved in both excitatory neurotransmission and synaptic plasticity in the central nervous system (CNS). Lockhart, et al., Brain Res. 630:32-40 (1993). EAAs, however, are also neurotoxic and have been believed to be involved in an important mechanism associated with neuronal injury and death. Indeed, EAAs have been implicated in both acute traumatic events, such as stroke-induced hypoxia or ischemia, and chronic neuro-degenerative diseases, such as Huntington's Chorea and Alzheimer's disease. Farougui, et al., Brain Res. Rev. 16:171-191 (1991).
The agonist-induced overactivation of the N-methyl-D-asparate (NMDA) receptor by EAAs is believed to be the principal factor underlying the neurotoxic effect. The activation of the NMDA receptor by EAAs induces an influx of sodium and calcium ions into the cells, which results in neuronal death. Choi, et al., J. Neurosci. 7:369-379 (1987).